<p>Protein phosphorylation, which plays a key role in most cellular activities, is a reversible process mediated by protein kinases and phosphoprotein phosphatases. Protein kinases catalyse the transfer of the gamma phosphate from nucleotide triphosphates (often ATP) to one or more amino acid residues in a protein substrate side chain, resulting in a conformational change affecting protein function. Phosphoprotein phosphatases catalyse the reverse process. Protein kinases fall into three broad classes, characterised with respect to substrate specificity [<cite idref="PUB00005115"/>]:</p><p> <ul> <li>Serine/threonine-protein kinases</li><li>Tyrosine-protein kinases</li><li>Dual specific protein kinases (e.g. MEK - phosphorylates both Thr and Tyr on target proteins)</li> </ul> </p><p>Protein kinase function has been evolutionarily conserved from <taxon tax_id="562">Escherichia coli</taxon> to human [<cite idref="PUB00020114"/>]. Protein kinases play a role in a multitude of cellular processes, including division, proliferation, apoptosis, and differentiation [<cite idref="PUB00015362"/>]. Phosphorylation usually results in a functional change of the target protein by changing enzyme activity, cellular location, or association with other proteins. The catalytic subunits of protein kinases are highly conserved, and several structures have been solved [<cite idref="PUB00034898"/>], leading to large screens to develop kinase-specific inhibitors for the treatments of a number of diseases [<cite idref="PUB00034899"/>].</p><p>Eukaryotic protein kinases [<cite idref="PUB00001071"/>, <cite idref="PUB00001530"/>, <cite idref="PUB00003568"/>, <cite idref="PUB00003569"/>, <cite idref="PUB00005115"/>] are enzymesthat belong to a very extensive family of proteins which share a conserved catalytic core common withboth serine/threonine and tyrosine protein kinases. There are a number of conserved regions in thecatalytic domain of protein kinases. In the N-terminal extremity of the catalytic domain there is aglycine-rich stretch of residues in the vicinity of a lysine residue, which has been shown to be involvedin ATP binding. In the central part of the catalytic domain there is a conserved aspartic acid residuewhich is important for the catalytic activity of the enzyme [<cite idref="PUB00005145"/>].</p> Serine/threonine-protein kinase domain